AUTHOR AND EDITOR INFORMATION

Section 1 of 12  

• Authors and Editors
• Introduction
• Indications
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• Further Reading
• Acknowledgments
• References

INTRODUCTION

Section 2 of 12  

• Authors and Editors
• Introduction
• Indications
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• Further Reading
• Acknowledgments
• References

Partial cystectomy, also known as segmental resection of the bladder, is a surgical method of removing a selected full-thickness portion of the bladder wall. Once a more practiced technique, advances in transurethral resection of bladder tumors and accumulated knowledge of the natural history of bladder cancer have resulted in partial cystectomy being performed less frequently (see Table 1).

Partial cystectomy is used to treat both malignant and benign conditions of the bladder. Its primary malignant indication is for solitary, primary, muscle-invasive, or high-grade bladder cancer that does not involve the bladder trigone, vesical neck, or posterior urethra and that can be resected with adequate surgical margins (minimum of 2 cm). Other indications for partial cystectomy include an inability to resect tumors transurethrally, a need for adequate biopsy of radiation-induced ulcerations, the presence of a tumor in a bladder diverticulum, patient choice, palliation of severe local symptoms, preservation of native bladder function and continence, and poor surgical risk for more aggressive procedures such as cystectomy. Adenocarcinomas and urachal carcinomas develop mostly in the dome of the bladder and may be amenable to partial cystectomy.

A few benign conditions of the bladder can be managed with partial cystectomy. These include resection of bladder diverticula, cavernous hemangiomas, ulcerative interstitial cystitis, colovesical fistula, vesicovaginal fistula, and localized endometriosis of the bladder.

Partial cystectomy has certain advantages over radical cystectomy, such as preserving a functional continent native urinary reservoir and sparing of potency in males. In addition, because a separate urinary diversion procedure (as is necessary in radical cystectomy) is not performed, some surgeons view partial cystectomy as a less morbid operation, suited for high-risk patients and palliative situations. The main disadvantage of partial cystectomy lies in the high historical local recurrence rates of bladder cancer, with only part of a globally diseased urothelium addressed. However, in properly selected patients, the results of partial cystectomy rival those of radical cystectomy. This review focuses on the current applications and indications for partial cystectomy, with an emphasis on the treatment of bladder cancer.

History of the Procedure

Table 1. Proportion of Patients With Bladder Cancer Treated With Partial Cystectomy
 

Frequency

Based on the National Cancer Institutes SEER Cancer Statistics Review, 67,160 new cases of bladder cancer will be diagnosed in 2007, and 13,750 persons will die from the disease. Currently, the overall male-to-female patient ratio is approximately 4:1. The ratio of bladder cancer in whites compared with African Americans is 1.5-2.1:1. The median age of patients is 73 years at time of diagnosis, with incidence and mortality per pathologic grade increasing as a function of age. Since 1950, the incidence of bladder cancer has increased by 50%, but the overall mortality rate (primarily in men) has decreased by 33%.

Etiology

The etiology of bladder cancer, a frequent indication for bladder resection, is unknown. Postulated theories include environmental carcinogens (eg, chemicals, ultraviolet light, radiation), aberration of normal cell growth regulation (eg, oncogene induction, suppressor gene negation), and abnormalities in the genetic composition of malignant cells.

Chemical exposures that may increase the risk of bladder cancer include aromatic amines, dietary nitrites, and nitrates. These include aniline dyes (eg, 2-naphthylamine, 4-aminobiphenyl, 4-nitrobiphenyl, 4-4-diaminobiphenyl [benzidine], 2-amino-1-naphthol), combustion gases, coal soot, chlorinated aliphatic hydrocarbons, and acrolein dyes. Smoking is associated with an up to 4-fold increase in the risk of bladder cancer. Other implicated factors include coffee and tea, phenacetin (an analgesic), chronic cystitis, the presence of chronic indwelling catheters, bladder calculi, pelvic irradiation, and exposure to cyclophosphamide. Schistosomiasis of the urinary bladder is associated with a higher incidence of squamous cell carcinoma. Currently, no evidence links bladder cancer to heredity.

Recent investigations have addressed the arsenic content of drinking water. International studies in Taiwan, Chile, and Argentina have suggested that as little as 10.1 mcg/L of arsenic in drinking water increases the risk.^{9, 10} In Taiwan, population studies of 8102 residents found that concentrations of 10-50, 50-100, and more than 100 mcg/L of arsenic in drinking water (compared with levels <10 mcg/L) increase the relative risk of developing transitional cell carcinoma to 1.9, 8.2, and 15.3, respectively.⁹ In Chile, studies of arsenic levels from 100-570 mcg/L revealed an elevated standardized mortality ratio of bladder cancer of 6 in men and 8.2 in women.¹⁰ In the United States, estimates indicate that 350,000 persons are exposed to arsenic levels of more than 50 mcg/L and that 2.5 million are exposed to levels higher than 25 mcg/L. In one study, the relative risk estimate for an average level of arsenic in US drinking water was 1 in 1000 persons.¹¹

Oncogenes and tumor suppressor genes implicated in bladder cancer include TP53, retinoblastoma gene (Rb), p15, and p16. Alterations in TP53, a normal tumor suppressor gene that is found on chromosome 17p and that controls apoptosis, lead to more aggressive bladder cancers. Ongoing studies are exploring the clinical implications of these tumor suppressor genes. Currently, conventional staging and grading are sufficient.

The tumor suppressor gene Rb is found on chromosome 13q. A mutated Rb gene or phosphorylated Rb gene leads to dissociation of its product protein, pRB, from the normally complexed transcription factor, E2F. Dissociated E2F drives the transition from G1 to S phase in cellular mitosis.

Two more protein regulators encoded on chromosome 9p, p15 and p16, inhibit nuclear cyclin-dependent kinases from phosphorylating pRB. When p15 and p16 mutate, they can no longer prevent phosphorylation of pRB, resulting in dissociation of the pRB-E2F complex, and free E2F is allowed to stimulate the cell's G1- to S-phase proliferation. Very aggressive high-grade bladder tumors have been associated with alterations in TP53. Mutations in Rb, p15, and p16 have been associated with low-grade superficial tumors.

Bladder cancer often behaves as a field disease; the entire urothelium, from the renal pelvis to the urethra, is susceptible to malignant transformation. Transitional carcinoma cells may also have the ability to migrate and implant at different sites along the urothelium.

Clinical

A thorough history should be obtained, and a thorough physical examination should be performed. In patients with bladder cancer, the most common presenting symptom is painless hematuria (85%). Hematuria is often intermittent; therefore, a single urinalysis finding may not be significant. Bladder irritability that manifests as urinary frequency, urgency, and dysuria is the second most common symptom. These symptoms rarely occur without hematuria (microscopic or gross). Flank pain due to ureteral obstruction, lower-extremity edema, and pelvic masses are other presenting symptoms. Symptoms of advanced disease, such as weight loss and abdominal or bone pain, are rare because patients usually seek medical attention before these develop.

INDICATIONS

Section 3 of 12  

• Authors and Editors
• Introduction
• Indications
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• Further Reading
• Acknowledgments
• References

Indications for Malignancy

Bladder cancer

Partial cystectomy is suitable to treat tumors that meet strict criteria, including (1) no prior history of bladder cancer, (2) no malignancy (eg, carcinoma in situ or papillary tumors) distant from the known bladder cancer, (3) a solitary muscle-invasive tumor located well away from the ureteral orifices that is amenable to partial cystectomy (ie, 2 cm of normal bladder around the lesion), (4) a reasonable expectation that the residual postoperative bladder will have adequate capacity and compliance to ensure functionality, and (5) ideally, partial cystectomy should be used for T1-T2b tumors. Additionally, higher-stage tumors with deeper invasion (eg, T3 and above) found during surgery may benefit from complete resection if negative surgical margins can be obtained. Adjuvant chemotherapy (eg, cisplatin-based) and/or radiation (currently up to 65 Gy) may provide additional local control for T3b tumors or tumors that have been found to penetrate through perivesical fat.

High-grade lesions can be managed with partial cystectomy if they meet the above criteria. The most common lesions amenable to partial cystectomy include grade II and III tumors located away from the base and trigone of the bladder (ie, on the lateral walls or dome of the bladder). A bimanual examination should be performed under anesthesia to confirm resectability.

Cancers in bladder diverticula

Diverticular cancers comprise 1.5-10% of all bladder cancers are more likely to penetrate the bladder wall because of the relatively thin nature of the wall and its muscular layers. Transurethral resection of the tumor, if possible, is a viable option. However, inadvertent perforation of the diverticulum is a definite risk because of the paucity of muscular fibers in the diverticulum and may lead to dissemination of urothelial cancer cells. Bladder diverticula are usually resected with partial cystectomy. Previous reports suggested a high rate of recurrence and poor prognosis for diverticular tumors. However, more recent data suggest that complete tumor excision via conservative means with or without adjuvant intravesical therapy carries a 5-year disease-specific survival rate of 70%. This is much better than previously reported.

Partial cystectomy and other cancers

In appropriate cases, cancer that invades the bladder from the nearby rectum, colon, prostate, uterus, cervix, or ovaries has been treated with partial cystectomy. Locally invasive colorectal carcinoma that involves the bladder has traditionally been treated with total pelvic exenteration; when possible, bladder-sparing techniques, such as partial cystectomy, have yielded a local recurrence rate of 17% and a 3-year survival rate of 39-74%, provided surgical margins are clear of disease.

Adenocarcinoma of the bladder, which includes urachal cancers, is often treated with partial cystectomy. Urachal lesions (20-40% of adenocarcinomas) are thought to arise from residual transitional cells that line the urachal remnant. The overall 5-year survival rate associated with urachal adenocarcinoma is poor (6-15%); however, recent evidence has shown that extended partial cystectomy with removal of the bladder segment, posterior rectus fascia, peritoneum, and umbilicus offers the best chance for survival. In a study by Dandekar et al, the 5-year survival rate after partial cystectomy of urachal adenocarcinoma was 56.3%.¹² Herr found that contained urachal adenocarcinomas that were completely resected using extended partial cystectomy had a favorable disease-free result rate (77%).¹³ Following partial cystectomy, cure rates of well-differentiated urachal adenocarcinomas approach 100%.

Rhabdomyosarcomas of the bladder comprise 17-50% of all genitourinary rhabdomyosarcomas, with nearly all embryonal subtypes occurring in children. These patients have also been successfully treated with partial cystectomy as an alternative to radical cystectomy or primary chemotherapy with local radiation. Disease-free survival rates have been found to be as high as 78.5% with a 2- to 16-year follow-up following partial cystectomy with or without neoadjuvant chemotherapy and radiation. Most of these patients were able to retain functional bladders, with minimal lower urinary tract symptoms.

Indications for Benign Conditions

A few benign conditions of the bladder can be managed with partial cystectomy. They include bladder diverticula (which are resected), cystic hydatid disease, cavernous hemangiomas, refractory interstitial cystitis, colovesical fistula, vesicovaginal fistula, and localized endometriosis of the bladder.

CONTRAINDICATIONS

Section 4 of 12  

• Authors and Editors
• Introduction
• Indications
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• Further Reading
• Acknowledgments
• References

In patients with malignancy, the entire urothelial tract must be evaluated before a partial cystectomy is performed. No evidence of disease elsewhere in the urinary tract must be demonstrated, including carcinoma in situ, transitional cell carcinoma, adenocarcinoma, squamous cell carcinoma, and severe urothelial dysplasia. This requires investigation of not only the bladder but also the kidneys and ureters.

Other contraindications to partial cystectomy include cellular atypia, prostatic or trigonal invasion, an inability to obtain adequate surgical margins, prior radiation therapy, inadequate bladder volume following resection, evidence of metastasis, and poor surgical risk. Some surgeons feel that partial cystectomy is associated with less morbidity than radical cystectomy because operating time is decreased, a urinary diversion with bowel manipulation is not necessary, and an extraperitoneal technique is possible in some cases. Some patients who cannot undergo radical cystectomy can undergo partial cystectomy. Others cannot undergo surgery of any type. These decisions are based on individual medical and surgical judgments and are tempered by patient choice.

WORKUP

Section 5 of 12  

• Authors and Editors
• Introduction
• Indications
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• Further Reading
• Acknowledgments
• References

Lab Studies

Laboratory evaluation is performed for diagnosis and surgical preparation. Diagnostic laboratory evaluation for urothelial cancer includes urinalysis, cytology, and urinary tumor marker levels.

• Urinalysis can be used to detect microscopic and gross hematuria.
• Conventional microscopic urine cytology may reveal tumor cells. Limitations of cytology include a false-negative rate of approximately 20%. Low-grade well-differentiated tumors can appear cytologically normal, accounting for some of this low specificity. In addition, well-differentiated tumors are thought to be more cohesive; thus, cytology has a lower yield. These two factors may account for the significant false-negative rate in cytological testing. The false-positive rate is approximately 1-12%, mostly because of urothelial atypia, inflammation, or changes associated with chemotherapy or radiation.
• Recently, other urinary tumor markers associated with urothelial neoplasia have been developed and studied. These include the bladder tumor antigen (BTA) stat test, BTA TRAK test, nuclear matrix protein 22 (NMP-22), fibrin degradation products (FDPs), telomerase, hyaluronic acid, cytokeratins, DNA aneuploidy, Lewis X antigen expression, vascular endothelial growth factor, fluorescent in situ hybridization (FISH), and immunocytology.
• • BTA assays are based on an antibody-detectable tumor marker that is used to detect BTA, a basement membrane antigen released when cancer cells are invading and breaking down basement membrane.
  • The BTA stat test is used to identify a protein similar to human complement factor H. Bladder cancer cells exhibit factor H, which interacts with complement C3b to inhibit the membrane attack complex and protects from immune attack.
  • NMP-22 is a nuclear matrix protein associated with DNA replication. Higher levels of NMP-22 have been found in the urine of patients with bladder cancer.
  • Bladder cancer cells produce vascular endothelial growth factor to support angiogenesis. This increases vessel wall permeability of blood and plasma proteins, such as plasminogen, fibrinogen, and other clotting factors. Escaped factors result in a fibrin clot that is broken down into FDPs, which are then released into the urine. Increased urinary levels of FDP have been observed in patients with bladder cancer.
  • FISH is a technique that involves fluorescently labeled DNA probes to assess cells for chromosomal alterations. FISH can be used to identify cells in the urine that have the chromosomal abnormalities consistent with transitional cell carcinoma. Studies of FISH reveal a sensitivity of 71-81% and a specificity of 94-96%.
• Although most of the new urinary markers yield a better sensitivity than conventional urinary cytology, their specificity is not as good. A recent comparison of the urinary markers reported a sensitivity of 44% for cytology, 74% for BTA stat, 53% for NMP-22, 52% for FDPs, and 70% for telomerase. The study reported a specificity of 95% for cytology, 73% for BTA stat, 60% for NMP-22, 91% for FDPs, and 99% for telomerase. The nuclear matrix protein BLCA-4 is the newest urinary tumor marker being investigated. An early study reports that this marker yields a sensitivity of 96% and a specificity of 81-100%.¹⁴

The general preoperative medical condition of the patient and the possible presence of metastatic disease should be assessed.

• Serum electrolytes help reveal any concomitant medical condition and help assess renal function.
• Blood reserves and bleeding risk can be determined with the help of a complete blood count, prothrombin time, and activated partial thromboplastin time.
• The presence of an infection can be investigated with a white blood cell count, urinalysis, and culture.
• Liver function tests and alkaline phosphatase may indicate liver and bone metastases.

Imaging Studies

Routine studies performed for staging bladder cancer include chest radiography, intravenous pyelography (IVP), CT scanning of the abdomen and pelvis, bone scan, and liver function tests. Mandatory preoperative imaging focuses on diagnosing and staging bladder cancer. Staging evaluation is a valuable tool to help determine whether the patient has superficial or muscle-infiltrating disease.

• Intravenous pyelography: IVP is required in all patients with cystoscopic evidence of bladder cancer. IVP enables evaluation of the collecting system of the kidneys, ureters, and bladder for any associated tumors. Retrograde pyelography during cystoscopy can serve as an alternative to IVP.
• CT urography: In recent years, CT urography has become a viable option to image the upper urinary tract. Some studies indicate the sensitivity and specificity of CT scanning surpasses that of IVP. Furthermore, many patients undergo CT scanning of the abdomen and pelvis as part of their staging evaluation (see Staging); thus, the upper urinary tract may be evaluated in the same setting.
• MRI
• • Gadolinium-enhanced and gadolinium-excreted MRI scans have also been used to image the renal pelvis and ureters. Whether MRI is as accurate as IVP or retrograde pyelography is currently under investigation.
  • MRI generally does not provide more information than a CT scan. If bone metastases are suspected, MRI is more sensitive for detection than a CT scan or a radionucleotide bone scan. Recent work on collecting system imaging with MRI is ongoing. In addition, recently published studies using ferumoxtran-10–enhanced MRI suggest that this modality may improve lymph node staging in patients with bladder cancer.
• Ureteroscopy: ureteroscopy can help directly visualize and allow for biopsy of any suspicious lesion in the ureter or renal collecting system. However, ureteroscopy is invasive.
• CT scanning
• • Aggressive imaging, such as CT scanning of the abdomen and pelvis and bone scans, is not necessary to evaluate superficial disease. These forms of imaging usually are reserved for documented invasive disease. CT scan itself may provide information regarding depth of tumor invasion, pelvic and paraaortic lymphadenopathy, and the presence of liver or adrenal metastases. CT scan may fail to detect nodal metastases in as many as 40% of patients. Liver metastases smaller than 2 cm in diameter likewise are difficult to detect. Also, CT scan can make only gross assessments of extravesical involvement.
  • Although CT scanning of the chest is the most sensitive in evaluating for pulmonary metastases, this modality CT reveals many lesions smaller than 1 cm in diameter that may represent calcified granulomas. Plain radiography of the chest is usually used instead because standard films usually reveal lesions larger than 1 cm.
• Bone scanning: This is not commonly performed in patients with normal alkaline phosphatase levels but may be performed as a baseline from which to compare future bone scans.
• Positron emission tomography (PET): Currently, PET scanning has a limited role in the evaluation of bladder cancer. PET scanning has shown promise in detecting lymph node metastasis or distant soft-tissue metastasis; however, because of the low urinary excretion of commonly used radioisotopes involved in PET scans, they are not yet helpful in the pelvic imaging of bladder cancer.

Diagnostic Procedures

• Cystoscopy should be performed in all patients in whom bladder cancer is suggested.
• Biopsy samples should be obtained from multiple sites (including the urethra) before partial cystectomy is considered.
• Retrograde pyelography can be performed at the same time if findings from an IVP or CT urography are inconclusive to adequately evaluate the upper urinary tracts. With the advances in endoscopic equipment and fiberoptics, ureteroscopy has enabled direct visual inspection of any suggestive upper-tract lesions, with the ability to obtain a biopsy specimen and even treat superficial lesions.
• Selective saline wash cytologies or brush biopsies may be performed for further evaluation of the upper tract.
• Transurethral resection with superficial and deep-muscle biopsy is an important tool to evaluate the depth of invasion and tumor pathology. Bladder perforation and possible spillage of tumor cells outside of the bladder should be avoided. However, recent evidence suggests that, even with extraperitoneal or intraperitoneal perforation, the risk of extravesical tumor seeding is low.
• Pelvic lymphadenectomy during cystectomy remains the most accurate way of determining disease in the lymphatic system. Primary regions of lymphatic spread of bladder cancer include the perivesical, hypogastric, obturator, external iliac, and presacral nodes. Boundaries of the lymphadenectomy include the iliac bifurcations, femoral canals, genitofemoral nerves, and the bladder pedicles. Lymphadenectomy may also provide a therapeutic benefit. Of the 10-40% of patients with lymph node metastases who present for radical cystectomy, 35-70% have only limited metastases and 10-35% may be cured with cystectomy and lymphadenectomy. Laparoscopic lymphadenectomy prior to primary tumor resection has not been standard practice.

Histologic Findings

Primary solitary bladder cancer is a common indication for consideration of partial cystectomy. More than 90% of bladder cancers are transitional cell carcinomas. Of these, 70% are papillary, 10% are nodular, and 20% are mixed. When confined to the urothelium, the cancer is called carcinoma in situ. The other 10% of tumors are composed predominantly of squamous cell carcinomas (3-7%) and adenocarcinomas (2%). Secondary metastatic disease in the bladder accounts for less than 1% of all bladder cancers.

Not uncommonly, multiple tumor types coexist in the same bladder. The most common combination is a high-grade papillary transitional cell carcinoma with carcinoma in situ. Elements of squamous cell carcinoma are also frequently found with transitional cell cancers. Adenocarcinomas and transitional cell carcinoma is a less common combination. Tumors that contain transitional cell elements are still classified as a transitional cell carcinoma.

Carcinoma in situ

Carcinoma in situ consists of poorly differentiated transitional cell carcinoma cells confined to the urothelium. Carcinoma in situ may be papillary or flat in architecture. These cells demonstrate poor intercellular cohesiveness; thus, urine cytopathology is a very sensitive test. Carcinoma in situ may be present in more than 25% of patients with high-grade superficial tumors and, thus, can exist concurrently with cancer found elsewhere in the bladder. When found, partial cystectomy is contraindicated.

Transitional cell carcinoma

Histopathology is used to grade bladder cancer tumors. No uniform grading system exists; most grading systems are based on the degree of anaplasia of the tumor cells. Usually, 3-4 grades are considered, corresponding to the level of cellular differentiation. Tumor grade strongly correlates with stage and prognosis.

Grades and descriptions of transitional cell carcinoma are as follows:

• Grade 0 - Papilloma with fewer than 7 epithelial cell layers and no abnormalities in histology
• Grade I - Well-differentiated thin fibrovascular stalks with a thickened urothelium that contain more than 7 cell layers and that exhibit slight anaplasia and pleomorphism; possible increased nuclear-to-cytoplasmic ratio and prominence of nuclear membrane; rare mitotic figures
• Grade II - Moderately differentiated, wider fibrovascular core, greater cell disturbance with loss of cellular polarity, higher nuclear-to-cytoplasmic ratio, nuclear pleomorphism and prominent nucleoli, and more frequent mitotic figures
• Grade III - Poorly differentiated, marked pleomorphism, high nuclear-to-cytoplasmic ratios, and frequent mitotic figures; cells that remain undifferentiated from basement membrane to surface

Squamous cell carcinoma

Histologically, squamous cell carcinomas are composed of keratinized islands that show various degrees of differentiation. Eccentric cellular aggregates known as squamous pearls also exist. Urinary cytopathology is less sensitive in detecting squamous cell carcinoma. Histologic tumor differentiation is less predictive of overall prognosis than it is for transitional cell carcinomas, although tumor stage shows a strong correlation with prognosis.

Adenocarcinoma

All histologic variants of enteric adenocarcinoma, including signet-ring and colloid variants, can be found in the bladder. Most adenocarcinomas are mucin-producing and are either papillary or solid in architecture. Signet-ring adenocarcinoma can produce linitis plastica of the bladder. Most adenocarcinomas are poorly differentiated and invasive upon presentation.

Staging

The American Joint Committee has designated staging based on the tumor, node, and metastases (TNM) classification.

• The TNM system for the primary tumor (T) is as follows:
• • Stage TX - Primary tumor cannot be assessed
  • Stage T0 - No evidence of primary tumor
  • Stage Ta - Noninvasive papillary carcinoma
  • Stage Tis - Carcinoma in situ
  • Stage T1 - Invades subepithelial connective tissue
  • Stage T2a - Invades superficial muscle (inner half)
  • Stage T2b - Invades deep muscle (outer half)
  • Stage T3a - Microscopic invasion of perivesical tissue
  • Stage T3b - Macroscopic invasion of perivesical tissue
  • Stage T4a - Invades prostate, uterus, and vagina
  • Stage T4b - Invades pelvic sidewall and abdominal wall
• The following is the TNM system for the regional lymph nodes (N). Note that regional lymph nodes are in the pelvis; all others are considered distant lymph nodes.
• • Stage NX - Regional lymph nodes cannot be assessed
  • Stage N0 - No regional lymph node metastasis
  • Stage N1 - Metastasis in a single lymph node, 2 cm or smaller in greatest dimension
  • Stage N2 - Metastasis in a single lymph node, larger than 2 cm but not larger than 5 cm in greatest dimension; or, multiple lymph nodes, none larger than 5 cm in greatest dimension
  • Stage N3 - Metastasis in a lymph node larger than 5 cm in greatest dimension
• The TNM system for distant metastasis (M) is as follows:
• • Stage MX - Distant metastasis cannot be assessed
  • Stage M0 - No distant metastasis
  • Stage M1 - Distant metastasis

While overstaging is relatively uncommon, clinical understaging occurs in as many as 53% of patients.

TREATMENT

Section 6 of 12  

• Authors and Editors
• Introduction
• Indications
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• Further Reading
• Acknowledgments
• References

Medical therapy

Bladder-sparing options other than partial cystectomy include monotherapy and multimodality protocols. Monotherapy consists of complete transurethral resection with or without repeat resections, systemic chemotherapy, or external beam radiation (XRT). Multimodality bladder-sparing therapy includes an initial transurethral resection followed by induction chemoradiation, repeat urological evaluation (biopsies or repeat transurethral resection), and, afterwards, consolidation chemoradiation. Salvage cystectomy is offered if no response to induction therapy is observed. 

Table 2. Comparison of Studies and Their Treatment Regimens and Results

^aMethotrexate, cisplatin, and vinblastine²⁴

Five-year survival rates following partial cystectomy vary from 35-80% (see Survival). Five-year survival rates following contemporary radical cystectomy are 50-60%. Multimodality bladder-sparing approaches yield 5-year survival rates of 48-56%, with 5-year bladder survival rates of 36-43%. These numbers, and particularly a direct comparison between the bladder-sparing approaches versus radical surgery, should be evaluated with caution because of patient-selection variables and a lack of prospective randomized trials.

Another concern with bladder-sparing protocols is that delaying cystectomy may risk disease progression. In addition, salvage radical cystectomy was eventually performed in 34-45% of cases,^{20, 22} with salvage cystectomy being a more difficult procedure than radical cystectomy without comorbid chemotherapy and pelvic radiation. Morbidity and quality-of-life concerns regarding chemotherapy and radiation must be weighed against those of radical cystectomy. Partial cystectomy, if successful, would have a theoretical upper hand over radical cystectomy or bladder-sparing chemoradiation protocols because it has the advantage of retaining the native bladder with none of the toxicities of chemotherapy or radiation. Urinary diversion after radical cystectomy also has advanced, with choices ranging from an ileal conduit to neobladders and continent catheterizable pouches.

The most important factors for bladder-sparing therapies include appropriate patient selection and long-term surveillance. Patient factors that increase risk of failure in transurethral resection/chemoradiation protocols include clinical stage higher than T2, associated ureteral obstruction with hydroureteronephrosis, incomplete initial transurethral resection, and lack of response to induction chemoradiation. Local recurrence rates for such protocols vary from 20-30%. Partial cystectomy also requires proper patient selection and long-term surveillance (see Indications and Recurrence).

Surgical therapy

Choices in the surgical management of bladder cancer include bladder-sparing or radical surgery. Bladder-sparing surgery includes techniques such as transurethral resection of bladder tumors (TURBT), with or without fulguration of such tumors, and partial cystectomy with or without pelvic lymph node dissection. Radical cystectomy involves more than just bladder excision. In men, it involves removal of the pelvic peritoneum, prostate, and seminal vesicles. In women, the urethra, uterus, broad ligaments, and anterior third of the vaginal wall are removed. Pelvic lymphadenectomy and urinary diversion are also performed. The remainder of this article discusses only partial cystectomy.

Preoperative details

In preparation for partial cystectomy, the bladder lesion is confirmed pathologically with initial transurethral resection. During resection, a thorough cystourethroscopy is performed and necessary biopsy samples collected to ensure that no other portions of the lower urinary tract contain disease. Appropriate imaging staging studies are performed (see Imaging Studies) to ensure that no disease exists elsewhere. Preoperative history, physical examination, medical assessment, and necessary laboratory evaluation (see Lab Studies) are also performed.

Intraoperative details

The patient is usually placed supine in a slight Trendelenburg position. Bimanual examination under anesthesia is performed to determine suitability for resection. A catheter is inserted through the urethra, and the bladder is irrigated with sterile water to decrease local tumor spillage. The bladder is left partially expanded by clamping the catheter, which facilitates dissection.

Generally, the partial cystectomy is approached in one of two different approaches—transperitoneal or extraperitoneal. The transperitoneal approach may be more suitable for tumors located posteriorly. Both approaches involve a lower midline or paramedian incision.

Modified pelvic lymph node dissection can be performed prior to partial cystectomy. This is usually approached from the obturator fossa to the iliac vessel bifurcation. The bladder is mobilized with the vas deferens and the obliterated hypogastric artery, and the superior vesical artery is divided and ligated. The superior vesical artery division is especially helpful in the lateral mobilization of the bladder to expose a posteriorly located lesion. The tumor is excised with a 2-cm margin, and perivesical fat and the overlying peritoneum are removed, if necessary, with care to protect both ureters and the rectum. If a 2-cm margin cannot be obtained from any ureter, radical cystectomy is suggested rather than ureteral reimplantation. Frozen sections of the specimen are sent for analysis to ensure negative surgical margins.

An alternative method of excision involves placement of a Satinsky clamp around the portion that contains the tumor, excision of the segment, and cauterization of the wound edges.

The bladder is closed in a 2-layer inverting fashion, and drains are placed in the perivesical space. A suprapubic tube is avoided because of possible tumor spread. Bladder drainage is managed with a temporary Foley catheter. Tumor spillage is detrimental and can be prevented via preoperative flushing of the bladder with sterile water, careful draping, isolation, and manipulation of the tumor. This protects wound edges, and the wound is copiously irrigated with sterile water prior to closure. Concurrent procedures, such as prostatic adenoma enucleation or transurethral incisions of the bladder neck for bladder outlet obstruction, should be avoided because of the risk of tumor implantation in the prostatic bed.

Postoperative details

Maintaining perivesical drainage facilitates visualization and aids in healing any urine leak from the bladder suture line. Drainage, either via an open Penrose drain or a closed Jackson-Pratt drain, is maintained until such leakage has stopped. A 20-22F urethral catheter is maintained postoperatively. This catheter serves to protect against urinary leakage and allows the bladder suture line to heal by maintaining low vesical pressures. It also provides access to the bladder, which allows for monitoring urine output and detecting any postoperative hematuria. This catheter is usually left in place for 7 days. Postoperative cystography prior to Foley removal is unnecessary.

Severe intravesical bleeding may result in urinary clot retention and may require gentle bladder irrigation to evacuate clots.

Wound and prevesical space infection may lead to abscesses that may require open or percutaneous drainage. Ureteral obstruction should be suspected if the patient reports flank pain. IVP or ultrasonography can be used to confirm this diagnosis, and percutaneous nephrostomy can temporarily divert urine in the hope that the obstruction is temporary.

Postoperative ureteral orifice edema may lead to an obstruction; however, this is only transient in nature. Incontinence due to altered bladder compliance and uninhibited bladder contractions usually improves with time and anticholinergic medications.

Follow-up

Bladder carcinoma is a recurrent disease. Careful monitoring of all patients is mandatory. Even superficial (Ta) high-grade (III) disease that has been successfully treated has shown a risk of eventual recurrence and progression, with 15-year progression-free and disease-specific survival rates of 61% and 74%, respectively. Those with low grade I superficial (Ta) lesions have a 15-year progression-free survival rate of 95%. Routine cystoscopy, initially every 3 months after resection, with voided urine cytologies should be performed.

Upper urothelial tract imaging with IVP, CT urography, or retrograde pyelography is are needed, although the upper tract requires less frequent monitoring than the lower urinary tract. Certainly, patients with T1 or more advanced disease and those with Ta high-grade disease must be monitored for disease recurrence and progression for life.

For excellent patient education resources, visit eMedicine's Cancer and Tumors Center. Also, see eMedicine's patient education article Bladder Cancer.

COMPLICATIONS

Section 7 of 12  

• Authors and Editors
• Introduction
• Indications
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• Further Reading
• Acknowledgments
• References

The overall complication rate of partial cystectomy is reported as 11-29%. Common complications of partial cystectomy include bleeding, infection, reduction of bladder capacity, and urinary extravasation. Other complications include fistulas (vesicocutaneous, vesicovaginal, colovesical), myocardial infarctions, pulmonary embolus, congestive heart failure, upper gastrointestinal hemorrhage, and death. Perioperative mortality rates once approached 10%; however, contemporary studies have not reported this rate. Local recurrences in the wound or suprapubic tract are worrisome complications that have been reported in 0-18% of patients.

OUTCOME AND PROGNOSIS

Section 8 of 12  

• Authors and Editors
• Introduction
• Indications
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• Further Reading
• Acknowledgments
• References

Recurrence

The major disadvantage of partial cystectomy compared with radical cystectomy is the issue of recurrence in the bladder. This implies a risk of disease progression, metastasis, and death from cancer. Recurrence rates associated with partial cystectomy have been reported as 19-78%. Relapses seem to be influenced by tumor stage T3b, poorly differentiated (grade III) tumors, and tumor size (>4 cm) rather than by the histologic subtype of the bladder cancer.

• Various studies and their corresponding recurrence rates are as follows:
• • Resnick and O'Connor (1973)²⁵ - 76%
  • Evans and Texter (1975)²⁶ - 40%
  • Novick and Stewart (1976)²⁷ - 50%
  • Peress et al (1977)²⁸ - 54%
  • Cummings et al (1978)²⁹ - 49%
  • Schoborg et al (1979)³⁰ - 70%
  • Faysal and Freiha (1979)³ - 78%
  • Jardin and Vallencien (1984)⁶ - 78%
  • Lindahl et al (1984)³¹ - 58%
  • Kaneti (1986)³² - 38%
  • Dandekar et al (1995)³³ - 43%
  • Holzbeierlein et al (2004)⁸ - 19%
  • Kassouf et al (2006)³⁴ - 49%

Peress et al noted that preoperative grade is an important prognostic factor in determining the risk of recurrence after partial cystectomy.²⁸ They studied 61 patients with stage A transitional cell carcinoma and found that 54% of patients with high-grade lesions experienced recurrence after partial cystectomy and eventually died of their disease. Recent work by Kassouf et al has shown that a higher pathological stage at time of partial cystectomy was associated with shorter recurrence-free survival. Older studies by Resnick and O'Connor and by Faysal and Freiha have also confirmed these findings.^{25, 3}

These high local recurrence rates reflect the natural history of bladder cancer. Transitional cell carcinoma of the bladder is thought to be a global disease of the urothelium. Recurrences and survival outcomes depend on tumor stage and grade. Conservative management of Ta-T2 disease with transurethral resection alone results in a 60% recurrence rate. Those with tumors prior to that have an 84% recurrence rate, with nearly half of all tumor recurrences being multifocal. Of all patients who initially present, two thirds have superficial (Ta, T1) disease, and two thirds of these patients experience recurrence (with 20% of the recurrences being of a higher grade). Death from transitional cell carcinoma occurs in 5% of patients with grade 1 disease, 16% of patients with grade II disease, 28-35% of patients with grade III/stage Ta disease, and 83% of patients with grade III/stage T2 disease.

Recurrences are treated in various ways. Transurethral resection and/or fulguration, intravesical chemotherapy, radiotherapy, repeat partial cystectomy, and radical cystectomy are all forms of treatment. Of all patients who undergo partial cystectomy as original therapy, 4-15% eventually undergo radical cystectomy with urinary diversion.

Survival

Many studies have examined the survival of patients with bladder cancer after partial cystectomy. Many have noted the relationship between tumor stage and grade and survival. Five-year survival rates varied from 35-80%; this compares with the 50-60% survival rate of a contemporary radical cystectomy series. Kassouf et al showed that patients undergoing partial cystectomy who had a prior history of superficial tumors had a decreased overall and advanced recurrence-free survival.³⁴ This finding is not surprising given that these patients have already demonstrated evidence of a global field effect within the urothelium. When rigid patient selection criteria are followed, partial cystectomy becomes a viable alternative to radical cystectomy.

Recent data from MD Anderson also suggests that adjuvant chemotherapy is associated with prolonged advanced recurrence-free survival.³⁴ However, no study has demonstrated that adjuvant chemotherapy offers any survival benefit over chemotherapy at the time of recurrence. Adjuvant chemotherapy should be considered in patients with extravesical extension or pelvic lymph node metastases who undergo partial cystectomy.

Table 3. Survival Rates by Tumor Grade

Table 4. Survival Rates by Tumor Stage

^aStage T3a/T3b

FUTURE AND CONTROVERSIES

Section 9 of 12  

• Authors and Editors
• Introduction
• Indications
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• Further Reading
• Acknowledgments
• References

Controversy still exists regarding combinations of chemotherapy or radiotherapy with or without bladder-sparing surgical techniques of partial cystectomy or transurethral resection versus traditional radical cystectomy. Newly evolving bladder-sparing protocols are currently being investigated as alternatives to radical surgery.

Studies on chemoradiative therapy involving agents such as methotrexate, vinblastine, doxorubicin (Adriamycin), and cisplatin (MVAC protocol) and bladder-sparing transurethral resection of tumor have shown that functional bladders can be preserved in 36-44% of patients at 5 years. The disease-specific 5-year survival rates range from 48-63%.

Newer agents currently being investigated include ifosfamide, gemcitabine, paclitaxel, and cisplatin combinations. These chemoradiative protocols will provide alternatives to radical cystectomy with urinary diversion.

When partial cystectomy is compared with radical cystectomy and the newer bladder-sparing protocols, partial cystectomy has advantages over radical cystectomy because it retains a functional native bladder. It also has the advantage over chemoradiative bladder-sparing techniques because it avoids the morbidity, mortality, toxicity, complexity, and expense of chemotherapy and radiation. In carefully selected patients, partial cystectomy seems to be the procedure of choice for muscle-invasive bladder cancer because its success rivals that of radical cystectomy. It also remains highly useful in various benign conditions. Future investigations are needed to define its evolving role.

FURTHER READING

Section 10 of 12  

• Authors and Editors
• Introduction
• Indications
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• Further Reading
• Acknowledgments
• References

For more information, see Medscape's Bladder Cancer Resource Center.

ACKNOWLEDGMENTS

Section 11 of 12  

• Authors and Editors
• Introduction
• Indications
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• Further Reading
• Acknowledgments
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Martin I Resnick, MD, to the development and writing of this article.

REFERENCES

Section 12 of 12

• Authors and Editors
• Introduction
• Indications
• Contraindications
• Workup
• Treatment
• Complications
• Outcome and Prognosis
• Future and Controversies
• Further Reading
• Acknowledgments
• References

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